AB0157 EFFICACY AND SAFETY OF FILGOTINIB IN ACTIVE RHEUMATOID ARTHRITIS PATIENTS WITH INADEQUATE RESPONSE TO METHOTREXATE: COMPARATIVE STUDY WITH FILGOTINIB AND TOCILIZUMAB EXAMINED BY CLINICAL INDEX AS WELL AS MUSCULOSKELETAL ULTRASOUND ASSESSMENT (TRANSFORM STUDY): STUDY PROTOCOL
Authors: T. Shimizu, S. Y. Kawashiri, S. Morimoto, Y. Kawazoe, S. Kuroda, R. Kawasaki, Y. Ito, S. Sato, H. Yamamoto, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2022)

Background The administration of Janus kinase (JAK) inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved even the clinical outcomes in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX). The dysregulation of JAK- signal transducer and activator of transcription (STAT) pathways via overproduction of cytokines, such as interleukin-6 (IL-6) is involved in the pathogenesis of RA (1). Filgotinib, a preferential JAK1 inhibitor, is effective in suppressing disease activity and preventing the progression of joint destruction due to inhibition of the JAK-STAT pathway. IL-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways due to inhibition of IL-6 signaling. Thus, it should be desirable to investigate whether the effectiveness of filgotinib monotherapy is non-inferior to those of tocilizumab monotherapy in RA patients with inadequate response to MTX. In addition, it is important to accurately evaluate disease activity at the joint level by using musculoskeletal ultrasound (MSUS) and clinical disease activity indices, including subjective parameters (2). Objectives This study’s principal objective is to evaluate the effects of filgotinib monotherapy is non-inferior to those of tocilizumab monotherapy in RA patients with inadequate response to MTX. In addition, we will evaluate changes in patients’ parameters, including clinical disease activity indices, MSUS scores, serum biomarkers, patient-reported outcome (PRO), and modified total Sharp score (mTSS) after the administration of filgotinib or tocilizumab. Herein, we describe the study protocol for this study. Methods This study is an interventional, multicenter, randomized, open-label, parallel-group and non-inferiority clinical trial with a 52-week follow-up. In total, 400 RA patients with at least moderate disease activity during treatment with MTX will be included. Patients will be randomized in a 1:1 ratio to administration of filgotinib 200mg/day monotherapy or subcutaneous tocilizumab 162mg/biweekly monotherapy switched from MTX (Figure 1). We will evaluate disease activity by measuring clinical disease activity indices and by using MSUS. The primary endpoint is the proportion of patients who achieve an American College of Rheumatology 50 response at week 12. Important secondary endpoints are the changes from the baseline of the MSUS scores, PRO, and mTSS. We will also comprehensively analyze the serum levels of multiple biomarkers such as cytokines and chemokines. Figure 1. Results Although the study results cannot be shown because the research entry is in progress, they are expected to show the non-inferiority of filgotinib monotherapy to tocilizumab monotherapy in RA patients with inadequate response to MTX. Conclusion The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS, which accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. In addition, we will evaluate the effectiveness of both drugs by integrating multilateral assessments, i.e., clinical disease activity indices, MSUS findings, and serum biomarkers. References [1]Gadina M, Le MT, Schwartz DM, Silvennoinen O, Nakayamada S, Yamaoka K, et al. Janus kinases to jakinibs: from basic insights to clinical practice. Rheumatology (Oxford). 2019;58(Suppl 1):i4-i16. [2]Colebatch AN, Edwards CJ, Ostergaard M, van der Heijde D, Balint PV, D’Agostino MA, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14. Disclosure of Interests Toshimasa Shimizu: None declared, Shin-ya Kawashiri: None declared, Shimpei Morimoto: None declared, Yurika Kawazoe: None declared, Shohei Kuroda: None declared, Rina Kawasaki: None declared, Yasuko Ito: None declared, Shuntaro Sato: None declared, Hiroshi Yamamoto: None declared, Atsushi Kawakami Grant/research support from: Gilead Sciences, Inc.